TY - JOUR
T1 - Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer
T2 - A phase 1b JAVELIN solid tumor study
AU - Dirix, Luc Y.
AU - Takacs, Istvan
AU - Jerusalem, Guy
AU - Nikolinakos, Petros
AU - Arkenau, Hendrik Tobias
AU - Forero-Torres, Andres
AU - Boccia, Ralph
AU - Lippman, Marc E.
AU - Somer, Robert
AU - Smakal, Martin
AU - Emens, Leisha A.
AU - Hrinczenko, Borys
AU - Edenfield, William
AU - Gurtler, Jayne
AU - von Heydebreck, Anja
AU - Grote, Hans Juergen
AU - Chin, Kevin
AU - Hamilton, Erika P.
N1 - Funding Information:
Conflict of interest GJ Reports honoria from Novartis, Celgene, and Roche; consulting/advisory roles for Novartis and Celgene; research funding from Novartis, MSD, and Roche; travel, accommodations, expenses from Novartis, Roche, and GSK. AFT reports research funding (to institution) from Pfizer. RB reports honoraria from Amgen, Cel-gene, AstraZeneca, and Tesaro; consulting/advisory role, speaker’s bureau fees, and travel, accommodations, and expenses for Heron Therapeutics. ML reports a leadership role and stock or other ownership for Seattle Genetics, Oncology analytics, and Geneyus. LE reports travel, accommodations, or expenses from Bayer Pharmaceuticals; consulting/advisory roles for Celgene, Vaccinex, Amgen, AstraZeneca, Syn-dax, Peregrine, eTHeRNA, Bayer, Molecuvax, and Gritstone; research funding from Genentech, Roche, EMD Serono, MaxCyte, MSD, As- traZeneca, Aduro Biotech, and Corvus; and is an SGE to the FDA. BH reports consulting/advisory roles for Bayer, Gilead, and Biotheranos-tics and research funding from EMD Serono, MedImmune, and Astra-Zeneca. WE participated in speakers’ bureau for Astellas and Mediva-tion. JG reports research funding from EMD Serono. AvH and HJG are employees at Merck KGaA, Darmstadt, Germany. KC is an employee of EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany. EH reports research funding (to institution) from Sarah Cannon Research Institute. All other authors have nothing to disclose.
Funding Information:
Acknowledgements We thank the patients and their families, investigators, coinvestigators, and the study teams at each of the participating centers and at Merck KGaA, Darmstadt, Germany and EMD Serono Research & Development Institute, Inc., Billerica, MA, USA (a business of Merck KGaA, Darmstadt, Germany). This trial was sponsored by Merck KGaA, Darmstadt, Germany and is part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer, Inc., New York, NY, USA. Medical writing support was provided by Clini-calThinking, Inc., Hamilton, NJ, USA and funded by Merck KGaA, Darmstadt, Germany and Pfizer, New York, NY, USA.
Funding Information:
We thank the patients and their families, investigators, coinvestigators, and the study teams at each of the participating centers and at Merck KGaA, Darmstadt, Germany and EMD Serono Research & Development Institute, Inc., Billerica, MA, USA (a business of Merck KGaA, Darmstadt, Germany). This trial was sponsored by Merck KGaA, Darmstadt, Germany and is part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer, Inc., New York, NY, USA. Medical writing support was provided by Clini-calThinking, Inc., Hamilton, NJ, USA and funded by Merck KGaA, Darmstadt, Germany and Pfizer, New York, NY, USA. Funding Merck KGaA, Darmstadt, Germany and Pfizer, Inc.
Publisher Copyright:
© The Author(s) 2017.
PY - 2018/10/23
Y1 - 2018/10/23
N2 - Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). Results A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Conclusion Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.
AB - Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). Results A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2–50 weeks and followed for 6–15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1− tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Conclusion Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.
KW - Avelumab
KW - Metastatic breast cancer
KW - PD-L1
KW - Second-line
KW - Triple-negative breast cancer
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U2 - 10.1007/s10549-017-4537-5
DO - 10.1007/s10549-017-4537-5
M3 - Article
C2 - 29063313
AN - SCOPUS:85031927832
VL - 167
SP - 671
EP - 686
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 3
ER -